ABSTRACT

BACKGROUND: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers.

METHODS: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC.

RESULTS: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013).

CONCLUSIONS: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

PMID:37744425 | PMC:PMC10515528 | DOI:10.1177/11795549231195293

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PubMed articles on: Cardio-Oncology

Galectin-3 contributes to acute cardiac dysfunction and toxicity by increasing oxidative stress and fibrosis in doxorubicin-treated mice

Int J Cardiol. 2023 Sep 22:131386. doi: 10.1016/j.ijcard.2023.131386. Online ahead of print.

ABSTRACT

BACKGROUND: Doxorubicin (DOX) leads to cardiovascular toxicity through direct cardiomyocyte injury and inflammation. We aimed to study the role of Galectin-3 (Gal-3), a β-galactosidase binding lectin associated with inflammation and fibrosis in DOX-induced acute cardiotoxicity in mice.

METHODS: Male C57 and Gal-3 knockout (KO) mice were given a single dose of DOX (15 mg/kg, i.p) or placebo. Serum creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and cardiac thiobarbituric acid-reactive substance (TBARS) were measured at 3 days to assess cardiac injury and oxidative stress. Cardiac remodeling and function were studied by echocardiography and catheterization at 7 days. Myocardial fibrosis was quantified in picrosirius red stained slices.

RESULTS: Absence of Gal-3 tended to reduce the mortality after DOX. DOX significantly increased CPK, LDH, AST and TBARS while treated Gal-3 KO mice showed reduced injury and oxidative stress. After 7 days, adverse remodeling, fibrosis and dysfunction in treated-C57 mice were severely affected while those effects were prevented by absence of Gal-3.

CONCLUSION: In summary, genetic deletion of Gal-3 prevented cardiac damage, adverse remodeling and dysfunction, associated with reduced cardiac oxidative stress and fibrosis. Understanding the contribution of GAL-3 to doxorubicin-induced cardiac toxicity reinforces its potential use as a therapeutic target in patients with several cancer types.

PMID:37741348 | DOI:10.1016/j.ijcard.2023.131386

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PubMed articles on: Cancer & VTE/PE

Real-world data emulating randomized controlled trials of non-vitamin K antagonist oral anticoagulants in patients with venous thromboembolism

BMC Med. 2023 Sep 29;21(1):375. doi: 10.1186/s12916-023-03069-1.

ABSTRACT

BACKGROUND: Emulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE).

METHODS: Five landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel-Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates.

RESULTS: Compared to trial populations, real-world study populations were older (range: 63-69 years [RWE] vs. 54-59 years [RCT]), with more females (55-60.5% vs. 39-48.3%) and had a higher prevalence of active cancer (4.2-15.4% vs. 2.5-9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70-0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37-0.96; Hokusai-VTE: 0.49, 0.31-0.78; EINSTEIN-DVT: 0.54, 0.33-0.89; EINSTEIN-PE: 0.50, 0.34-0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs.

CONCLUSIONS: This study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.

PMID:37775786 | PMC:PMC10542685 | DOI:10.1186/s12916-023-03069-1

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PubMed articles on: Cancer & VTE/PE

Are Antibiotics the New Appendectomy?

Cureus. 2023 Sep 1;15(9):e44506. doi: 10.7759/cureus.44506. eCollection 2023 Sep.

ABSTRACT

Prior to the development of laparoscopic procedures, open appendectomy was the standard of care for the majority of appendicitis cases. Recently, studies have debated using antibiotics as a first-line treatment in uncomplicated appendicitis cases. The definition of uncomplicated appendicitis is not always clear-cut; however, with the large-scale accessibility of radiologic techniques, it is becoming increasingly easier to classify patient groups. As suggested by clinical and radiological patient data, this has raised the speculation of considering antibiotic therapy as the sole treatment modality in uncomplicated appendicitis cases. We aim to compare the options of surgery and antibiotics only in terms of efficacy, complications, and financial cost. A range of databases and search strategies were adopted, and various databases were used, including PubMed, ScienceDirect, Google Scholar, and JAMA. Collectively, 30 studies were reviewed, but only 18 were included. Efficacy rates were higher in the appendectomy group. Nevertheless, the antibiotics-only group maintained an efficacy rate greater than 70% at one-year follow-up. Risk factors that decreased the efficacy in medical management included the presence of appendicolith, neoplasm, appendiceal dilatation, peri-appendiceal fluid collection, higher mean temperature, CRP, and bilirubin. Complications were more frequent and significant in the surgery group. These included complications related to anaesthesia, surgical site infections, damage to nearby structures, and pulmonary embolism. Despite several years of follow-up and disease recurrences, higher financial costs were observed in surgically treated patients compared to the antibiotics-only group. Given the high success rates post-appendectomy for acute appendicitis over the decades, the efficacy of conservatively treated acute appendicitis raises a strong argument when choosing one of the two options. The efficacy remained consistently higher across the literature in the surgery group than in the antibiotics-only group. However, it is still arguable that antibiotics may be a preferable option given an efficacy rate of more than 70% at one year and overall higher complications associated with surgery. The argument of missing a neoplasm by avoiding surgery is valid. However, most are carcinoid neuroendocrine neoplasms with a low probability of metastasis (<5%)

PMID:37790034 | PMC:PMC10544542 | DOI:10.7759/cureus.44506

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PubMed articles on: Cancer & VTE/PE

D-Dimers Variability in the Perioperative Period of Breast Cancer Surgery Helps to Predict Cancer Relapse: A Single-Centre Prospective Study

Cancer Control. 2023 Jan-Dec;30:10732748231204713. doi: 10.1177/10732748231204713.